Immunoglobulin therapy
Immunoglobulin therapy is the use of a mixture of antibodies to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain–Barré syndrome, and certain other infections when a more specific immunoglobulin is not available. Depending on the formulation it can be given by injection into muscle, a vein, or under the skin. The effects last a few weeks.
Common side effects include pain at the site of injection, muscle pain, and allergic reactions. Other severe side effects include kidney problems, anaphylaxis, blood clots, and red blood cell breakdown. Use is not recommended in people with some types of IgA deficiency. Use appears to be relatively safe during pregnancy. Human immunoglobulin is made from human blood plasma. It contains antibodies against many viruses.
Human immunoglobulin therapy first occurred in the 1930s and a formulation for injection into a vein was approved for medical use in the United States in 1981. It is on the World Health Organization's List of Essential Medicines. Each formulation of the product is somewhat different. A number of specific immunoglobulin formulations are also available including for hepatitis B, rabies, tetanus, varicella infection, and Rh positive blood exposure.
Medical uses
Immunoglobulin therapy is used in a variety of conditions, many of which involve decreased or abolished antibody production capabilities, which range from a complete absence of multiple types of antibodies, to IgG subclass deficiencies, to other disorders in which antibodies are within a normal quantitative range, but lacking in quality – unable to respond to antigens as they normally should – resulting in an increased rate or increased severity of infections. In these situations, immunoglobulin infusions confer passive resistance to infection on their recipients by increasing the quantity/quality of IgG they possess. Immunoglobulin therapy is also used for a number of other conditions, including in many autoimmune disorders such as dermatomyositis in an attempt to decrease the severity of symptoms. Immunoglobulin therapy is also used in some treatment protocols for secondary immunodeficiencies such as human immunodeficiency virus, some autoimmune disorders, some neurological diseases some acute infections and some complications of organ transplantation.Immunoglobulin therapy is especially useful in some acute infection cases such as pediatric HIV infection and is also considered the standard of treatment for some autoimmune disorders such as Guillain–Barré syndrome. The high demand which coupled with the difficulty of producing immunoglobulin in large quantities has resulted in increasing global shortages, usage limitations and rationing of immunoglobulin.
Australia
The Australian Red Cross Blood Service developed their own guidelines for the appropriate use of immunoglobulin therapy in 1997. Immunoglobulin is funded under the National Blood Supply and indications are classified as either an established or emerging therapeutic role or conditions for which immunoglobulin use is in exceptional circumstances only.Subcutaneous immunoglobulin access programs have been developed to facilitate hospital based programs.
Human normal immunoglobulin was approved for medical use in Australia in May 2021.
Canada
The National Advisory Committee on Blood and Blood Products of Canada and Canadian Blood Services have also developed their own separate set of guidelines for the appropriate use of immunoglobulin therapy, which strongly support the use of immunoglobulin therapy in primary immunodeficiencies and some complications of HIV, while remaining silent on the issues of sepsis, multiple sclerosis, and chronic fatigue syndrome.European Union
Brands include HyQvia, Privigen, Hizentra, Kiovig, and Flebogamma DIF.In the European Union, human normal immunoglobulin is used in people whose blood does not contain enough antibodies, also known as immunoglobulins. It is used to treat the following conditions:
- primary immunodeficiency syndromes ;
- low levels of antibodies in the blood in people with chronic lymphocytic leukaemia or myeloma and who have frequent infections;
- low levels of antibodies in the blood in people before or after allogeneic haematopoietic stem cell transplantation ;
- chronic inflammatory demyelinating polyneuropathy. In this rare disease, the immune system works abnormally and destroys the protective covering over the nerves.
- congenital agammaglobulinaemia and hypogammaglobulinaemia ;
- common variable immunodeficiency;
- severe combined immunodeficiency;
- immunoglobulin-G-subclass deficiencies with recurrent infections;
- replacement therapy in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.
- primary immunodeficiency syndromes with impaired antibody production;
- hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukaemia, in whom prophylactic antibiotics have failed;
- hypogammaglobulinaemia and recurrent bacterial infections in plateau-phase-multiple-myeloma patients who failed to respond to pneumococcal immunisation;
- hypogammaglobulinaemia in patients after allogenic haematopoietic-stem-cell transplantation ;
- congenital acquired immune deficiency syndrome with recurrent bacterial infections.
- primary immune thrombocytopenia, in patients at high risk of bleeding or prior to surgery to correct the platelet count;
- Guillain–Barré syndrome, which causes multiple inflammations of the nerves in the body;
- Kawasaki disease, which causes multiple inflammation of several organs in the body.
United Kingdom
The United Kingdom's National Health Service recommends the routine use of immunoglobulin for a variety of conditions including primary immunodeficiencies and a number of other conditions, but recommends against the use of immunoglobulin in sepsis, multiple sclerosis, neonatal sepsis, and pediatric HIV/AIDS.United States
The American Academy of Allergy, Asthma, and Immunology supports the use of immunoglobulin for primary immunodeficiencies, while noting that such usage actually accounts for a minority of usage and acknowledging that immunoglobulin supplementation can be appropriately used for a number of other conditions, including neonatal sepsis, considered in cases of HIV, considered as a second line treatment in relapsing-remitting multiple sclerosis, but recommending against its use in such conditions as chronic fatigue syndrome, PANDAS until further evidence to support its use is found, cystic fibrosis, and a number of other conditions.Brands include:
- Alyglo
- Anthrasil
- Asceniv
- Bivigam
- Gammagard Liquid
- Hizentra
- Hyqvia
- Octagam
- Panzyga
- Qivigy
- Xembify
- Yimmugo
Side effects
Local side effects of immunoglobulin infusions most frequently include an injection site reaction, itching, rash, and hives. Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain.
Serious side effects of immunoglobulin infusions in infants, children, and adults include chest discomfort or pain, myocardial infarction, tachycardia, hyponatremia, hemolysis, hemolytic anemia, thrombosis, hepatitis, anaphylaxis, backache, aseptic meningitis, acute kidney injury, hypokalemic nephropathy, pulmonary embolism, and transfusion related acute lung injury. There is also a small chance that even given the precautions taken in preparing immunoglobulin preparations, an immunoglobulin infusion may pass a virus to its recipient. Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis.
IVIG has long been known to induce a decrease in peripheral blood neutrophil count, or neutropenia in neonates, and in patients with Idiopathic Thrombocytopenic Purpura, resolving spontaneously and without complications within 48 h. Possible pathomechanisms include apoptosis/cell death due to antineutrophil antibodies with or without neutrophil migration into a storage pool outside the blood circulation.
Immunoglobulin therapy interferes with the ability of the body to produce a normal immune response to an attenuated live-virus vaccine for up to a year, can result in falsely elevated blood glucose levels, and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection.